1. Field of the Invention
The invention relates to genetic markers to identify cancer patients who are at the high risk for developing distant metastasis or poor prognosis. The genetic markers can serve as target genes in cancer therapy including nasopharyngeal cancer, hepatic cancer, lung cancer, or uterine cervical cancer. The present invention further relates to a method for predicting a risk of distant metastasis and poor prognosis in cancer patients including nasopharyngeal cancer, liver cancer, lung cancer, or uterine cervical cancer.
2. The Prior Arts
The cancer mortality increased dramatically for the past twenty years in the world. Nasopharyngeal carcinomas (NPC) arise from the squamous epithelium lining the surface and crypts of the nasopharynx. According to World Health Organization, it accounts for 0.3% of malignancies in Europe and North America. However, it has a high incidence for Chinese in regions of southern China, Hong Kong, Taiwan, and Singapore. NPC appear to have a significant ethnic and geographical distribution. Recent studies have attributed the development of NPC to a complex interaction of genetic factors, environmental factors and viral infection. Some of the oncogenes and tumor suppressor genes may be mutated after long time accumulation, which causes the normal cells change to cancer cells.
The infection of Epstein-Barr virus was regarded as the main cause of NPC, which was based on studies of the genome or gene products of Epstein-Barr virus found in NPC tissues. However, that concentrated too much on Epstein-Barr virus found in NPC tissues.
Not all NPC cell lines contained Epstein-Barr virus, and only a fraction of cells were found to harbor Epstein-Barr virus in the positive cell lines. The results were in consistent with the biopsy specimens obtained from NPC patients. In addition, the non-transformed squamous metaplastic cells of nasopharyngx contain no Epstein-Barr virus. All these results show that Epstein-Barr virus is not the major cause for NPC development, which is also supported by the following facts: (1) the cells from samples of NPC cell line or NPC biopsy did not express receptors for Epstein-Barr virus; (2) part of the NPC cells from NPC biopsy expressed secretory component protein (SC protein), the receptor of IgA, but not the non-transformed squamous metaplastic cells in nasopharynx; (3) NPC cell line carrying IgA receptors can be infected by Epstein-Barr virus (EBV) through IgA anti-EBV-VCA, (4) the growth rate of NPC cells increased if infected with Epstein-Barr virus.
Recently, many genetic abnormalities in NPC tissues have been defined by genome-wide studies through the progress in molecular biology. It has been reported that the changes of tumor suppressor genes on chromosome 3p, 9p, 11q, 13q, 14q, and 16q and oncogenes on chromosome 8, 12 were important in NPC development. Many studies are focus on the alleles of the above mentioned chromosomes. For example, RASSFIA gene on chromosome 3p is regarded as a tumor suppressor gene for NPC. Only RASSFIA was studied deeply in the mechanism of NPC up to present. Nevertheless, the development of NPC is believed to have a multifactorial etiology, the main regulating mechanism remains to be elucidated.
The understanding of molecular mechanism in NPC development will contribute to the detection, prognosis, therapy and prevention of NPC. Though local control rate of NPC reached 90%, there is 30% to 40% of the late stage NPC patients having distant metastasis and local recurrences. The survival time was less than one year for those had distant metastasis. There is still no effective ways in predicting and treatment of distant metastasis of NPC. The studies in gene regulating mechanism of NPC and the identification of proper genetic markers for forecasting the risk of poor prognosis and distant metastasis, further to serve as target gene in cancer therapy is therefore important. In addition, application of the genetic markers of NPC in other cancers can be beneficial at the same time.